Genetic oncological and molecular epidemiological research on development and progression of the biliary tract cancer in Asia

分别在胆囊癌、慢性胆囊炎、黄色肉芽肿性胆囊炎（XGC）和正常胆囊的上皮和间质中检测COX的表达。正常胆囊上皮中COX-2的表达率明显高于间质。COX-2在癌灶非癌旁上皮的表达率不仅显著低于癌，而且显著低于慢性胆囊炎、XGC和正常胆囊。在间质中，肿瘤、慢性胆囊炎和XGC中COX-2的表达率明显高于正常胆囊。非癌性相邻间质癌的发生率明显低于癌性和XGC。我们的研究结果表明，胆囊中COX-2的表达可能受多种因素的调节，与癌变没有直接关系。肝吸虫感染相关肝内胆管癌（ICC）是泰国东北部的一种主要肝癌。为了阐明细胞遗传学，我们通过比较基因组杂交分析了这些癌症在全基因组范围内的DNA拷贝数异常。低分化癌比高分化癌在18p11位点有更频繁的染色体增加。在第1季度-p36（34%）和第21季度- 13季度（28%），拷贝数频繁减少。本研究发现的改变可能是肝内胆管癌伴慢性炎症的新基因和预后因素的候选。我们还发现泰国肝内胆管癌的微卫星不稳定性（microsatellite instability， MSI）被归类为低频MSI， DNA MMR系统通过hMSH2和hMLH1基因突变在其癌变中不起主要作用。

The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis.The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. To elucidate cytogenetic, we analyzed DNA copy number abnormalities of these cancers in genome-wide scale by comparative genomic hybridization. Poorly-differentiated carcinomas have more frequent chromosomal gain at 18p11 than well-differentiated carcinomas. Frequent decrease in copy number were observed at 1pter-p36 (34%) and 21q13-qter (28%). Alterations found in this study might be candidate for novel genes and prognostic factors in the intrahepatic bile duct cancer with chronic inflammation. We also found that the microsatellite instability (MSI) of intrahepatic cholangiocarcinoma in Thailand, was classified as low frequency MSI and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis.